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dc.contributor.authorChi, Xin-Zi
dc.contributor.authorKim, Jiyeon
dc.contributor.authorLee, Yong-Hee
dc.contributor.authorLee, Jung-Won
dc.contributor.authorLee, Kyeong-Sook
dc.contributor.authorWee, Hee-Jun
dc.contributor.authorKim, Wun-Jae
dc.contributor.authorPark, Woo-Yoon
dc.contributor.authorOh, Byung-Chul
dc.contributor.authorStein, Gary S.
dc.contributor.authorIto, Yoshiaki
dc.contributor.authorVan Wijnen, Andre J.
dc.contributor.authorBae, Suk-Chul
dc.date2022-08-11T08:10:57.000
dc.date.accessioned2022-08-23T17:26:13Z
dc.date.available2022-08-23T17:26:13Z
dc.date.issued2009-10-08
dc.date.submitted2011-01-11
dc.identifier.citationCancer Res. 2009 Oct 15;69(20):8111-9. Epub 2009 Oct 6. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-09-1057">Link to article on publisher's site</a>
dc.identifier.issn0008-5472 (Linking)
dc.identifier.doi10.1158/0008-5472.CAN-09-1057
dc.identifier.pmid19808967
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49590
dc.description.abstractThe p14(ARF)-MDM2-p53 pathway constitutes an effective mechanism for protecting cells from oncogenic stimuli such as activated Ras and Myc. Importantly, Ras activation induces p14(ARF) and often occurs earlier than p53 inactivation during cancer development. Here, we show that RUNX3, a tumor suppressor in various tumors including stomach, bladder, colon, and lung, is stabilized by Ras activation through the p14(ARF)-MDM2 signaling pathway. RUNX3 directly binds MDM2 through its Runt-related DNA-binding domain. MDM2 blocks RUNX3 transcriptional activity by interacting with RUNX3 through an acidic domain adjacent to the p53-binding domain of MDM2 and ubiquitinates RUNX3 on key lysine residues to mediate nuclear export and proteasomal degradation. Our data indicate that the lineage-specific tumor suppressor RUNX3 and the ubiquitous p53 protein are both principal responders of the p14(ARF)-MDM2 cell surveillance pathway that prevents pathologic consequences of abnormal oncogene activation.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19808967&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1158/0008-5472.CAN-09-1057
dc.subjectApoptosis
dc.subjectBlotting, Western
dc.subjectCell Transformation, Neoplastic
dc.subjectCells, Cultured
dc.subjectCore Binding Factor Alpha 3 Subunit
dc.subjectinhibitors
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectImmunoprecipitation
dc.subjectKidney
dc.subjectMutation
dc.subjectProto-Oncogene Proteins c-mdm2
dc.subjectRNA, Small Interfering
dc.subjectTranscription, Genetic
dc.subjectTranscriptional Activation
dc.subjectTransfection
dc.subjectTumor Suppressor Protein p14ARF
dc.subjectTumor Suppressor Protein p53
dc.subjectUbiquitination
dc.subjectUbiquitins
dc.subjectras Proteins
dc.subjectCell Biology
dc.titleRunt-related transcription factor RUNX3 is a target of MDM2-mediated ubiquitination
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume69
dc.source.issue20
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/26
dc.identifier.contextkey1724066
html.description.abstract<p>The p14(ARF)-MDM2-p53 pathway constitutes an effective mechanism for protecting cells from oncogenic stimuli such as activated Ras and Myc. Importantly, Ras activation induces p14(ARF) and often occurs earlier than p53 inactivation during cancer development. Here, we show that RUNX3, a tumor suppressor in various tumors including stomach, bladder, colon, and lung, is stabilized by Ras activation through the p14(ARF)-MDM2 signaling pathway. RUNX3 directly binds MDM2 through its Runt-related DNA-binding domain. MDM2 blocks RUNX3 transcriptional activity by interacting with RUNX3 through an acidic domain adjacent to the p53-binding domain of MDM2 and ubiquitinates RUNX3 on key lysine residues to mediate nuclear export and proteasomal degradation. Our data indicate that the lineage-specific tumor suppressor RUNX3 and the ubiquitous p53 protein are both principal responders of the p14(ARF)-MDM2 cell surveillance pathway that prevents pathologic consequences of abnormal oncogene activation.</p>
dc.identifier.submissionpathstein/26
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages8111-9


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